Abstract
BACKGROUND AND AIMS: Sickle cell disease (SCD) is a genetic disorder characterized by intrinsic clinical manifestations, frequently exacerbated by vaso-occlusive episodes (VOEs), which significantly affect hematological parameters. This systematic review and meta-analysis is aimed at synthesizing evidence from studies published over the past 25 years on complete blood count profiles in SCD patients, both in the steady state and during VOEs. The objective was to clarify hypotheses and highlight the need for prospective studies to establish specific reference values for steady-state SCD patients, thereby improving patient management. MATERIALS AND METHODS: In accordance with the PRISMA guidelines and the Cochrane Handbook, a systematic search of major databases (including PubMed, Web of Science, and Google Scholar) was conducted to identify analytical studies published between 2000 and 2025. Eligible studies compared complete blood count profiles in SCD patients during VOEs and in the steady state. Study selection and data extraction were performed independently by two reviewers, with disagreements resolved by consensus. Extracted data were entered into Microsoft Excel 2013 and analyzed using R statistical software (Version 4.3.2). Between-study heterogeneity was evaluated using Higgins' inconsistency (Q) statistics, with results expressed as I(2) values and corresponding p values. The risk of bias in the included studies was assessed using the ROBINS-E tool. RESULTS: Eight studies met the inclusion criteria. Pooled analyses demonstrated a significant impact of VOEs on hemogram parameters. This impact was characterized by anemia and erythrocytopenia (standardized mean difference [SMD], random-effects model: -0.97 [-1.45; -0.50]), accompanied by microcytosis (SMD, random-effects model: 0.18 [-0.21; 0.58]) and hypochromia (SMD, random-effects model: -0.90 [-2.96; 1.15]). These changes were also associated with reduced fetal hemoglobin levels, increased red cell distribution width (RDW), and reticulocytosis. Regarding the white blood cell lineage, VOEs were associated with leukocytosis (SMD, random-effects model: 0.73 [0.23; 1.24]) and a moderate increase across leukocyte subpopulations. Concerning the platelet lineage, VOEs exerted variable effects on platelet production, ranging from negative to positive influences, with an overall increase in platelet count (SMDs, random-effects model: -0.17 [-1.13; 0.78] and 0.78 [0.53; 1.03], respectively), accompanied by reductions in mean platelet volume and platelet distribution width (PDW). CONCLUSION: This meta-analysis confirms the substantial influence of VOEs on red blood cell, white blood cell, and platelet parameters, as well as their associated indices. Importantly, although hematological parameters in the steady state are less severely altered than during VOEs, they often remain outside conventional reference ranges, reflecting a distinct physiological baseline in SCD patients. These findings underscore the urgent need for prospective studies to define specific hematological reference values for steady-state SCD patients, which is essential for optimizing their clinical management.